Role of SIRT6 in the pancreatic beta cell aging

SIRT6在胰腺β细胞衰老中的作用

基本信息

批准号：
10371337
负责人：
X Charlie Dong
金额：
$ 23.78万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-15 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10371337
关键词：
Age Age-Years Aging B Cell Proliferation B-Cell Development Beta Cell Biological Process Calcium Signaling Cell Aging Cell Death Cell membrane Cell physiology DNA Damage Data Deacetylase Defect Development Diabetes Mellitus Diet Disease Epigenetic Process Female Gene Expression Gene Expression Regulation General Population Genes Glucose Glucose Intolerance Guanosine Triphosphate Phosphohydrolases HDAC4 gene Histologic Homeostasis Human Impairment Insulin Intervention Islets of Langerhans Knock-out Knockout Mice Knowledge Life Literature Longevity Metabolic Metabolism Mission Mitochondria Modeling Molecular and Cellular Biology Monitor Monomeric GTP-Binding Proteins Mus Non-Insulin-Dependent Diabetes Mellitus Oxidative Stress Persons Phenotype Physiological Physiology Play Population Premature Mortality Prevalence Prevention Process Proteins Public Health Regulation Research Risk Factors Role Sirtuins Structure of beta Cell of islet Testing Transgenes Transgenic Mice United States National Institutes of Health age related anti aging base blood glucose regulation burden of illness cell age cell injury diabetes pathogenesis epigenetic regulation expectation gene function glucose metabolism high risk human old age (65+)improved innovation insight insulin secretion male middle age molecular phenotype mouse model new therapeutic target novel overexpression therapeutic development transgene expression voltage

项目摘要

Project Summary During aging, pancreatic beta cells undergo a decline in insulin secretion capacity, and this contributes to nearly 3-fold high diabetes prevalence in people aged over 65 years compared to the general population. Sirtuin 6 (SIRT6), a histone deacetylase, has been suggested to be a longevity factor. In the preliminary study, we have demonstrated that SIRT6 is required to maintain normal beta cell function and SIRT6 is downregulated in the beta cells during aging. Therefore, we hypothesize that SIRT6 plays an important role in the protection of pancreatic beta cells against aging-associated cellular damage. In this application, we will investigate the SIRT6 function and mechanism in the regulation of pancreatic beta cell aging. It is our expectation that the findings from this project will advance our understanding of the fundamental process of the aging of pancreatic beta cells and provide potential novel targets for the development of prevention and treatment of the age-related diabetes.

项目摘要在衰老期间，胰腺β细胞的胰岛素分泌能力下降，这与65岁以上的人相比一般人口。 Sirtuin 6（SIRT6）是一种组蛋白脱乙酰基酶，已被认为是寿命因子。在初步研究中，我们已经证明SIRT6需要维持正常的beta细胞衰老过程中β细胞中的功能和SIRT6在β细胞中下调。因此，我们假设Sirt6 在保护胰腺β细胞免受衰老相关的细胞中起重要作用损害。在此应用中，我们将研究SIRT6功能和机制胰腺β细胞衰老。我们期望这个项目的发现将推动我们的了解胰腺β细胞衰老的基本过程，并提供潜力预防和治疗年龄相关糖尿病的新目标。